INTRODUCTION — Patients who undergo hematopoietic cell transplantation (HCT) are subject to numerous complications in the first year after transplantation. These complications can affect many organ systems and they may influence the quality of life, duration of hospitalization, longer-term complications, and outcomes from transplantation.
This topic will address management of complications and functional recovery in the first year after autologous or allogeneic HCT.
Longer-term complications of HCT are discussed separately. (See "Long-term care of the adult hematopoietic cell transplantation survivor" and "Malignancy after hematopoietic cell transplantation".)
CONTRIBUTING FACTORS — Factors that affect the nature and severity of complications after HCT vary with the individual patient's circumstances. Factors that may contribute to early post-transplantation complications and the individual's reserves to tolerate them include:
●Prior cancer treatments (eg, chemotherapy, radiation therapy, immunotherapy)
●Status of the underlying cancer at the time of transplantation (eg, complete remission versus persistent disease)
●Comorbid medical conditions (eg, diabetes mellitus and hepatic, renal, cardiovascular, pulmonary conditions)
●Conditioning regimen (eg, myeloablative, reduced intensity, non-myeloablative)
●Donor source (eg matched sibling donor [MSD], matched unrelated donor [MUD], mismatched related or unrelated donor, haploidentical, and umbilical cord blood)
●Autologous versus allogeneic HCT
●Severity of graft-versus-host disease (GVHD), in patients who undergo allogenic HCT
●Duration and degree of cytopenias and immunosuppression
●Organ dysfunction (eg, liver, kidneys, heart, lungs)
MULTIDISCIPLINARY CARE — Specialists from many disciplines may be involved in the care of the patient who undergoes HCT, because treatment can affect nearly all organ systems. Communication and coordination of recommendations from various specialists are important to establish and sustain a successful care plan.
Optimal outcomes also require effective management of symptoms. A trial randomly assigned 160 adults undergoing autologous or allogeneic HCT for various hematologic malignancies to inpatient palliative care consultation versus usual transplant care [1]. At two weeks post-transplant, patients who received palliative care consultation had less depression, anxiety, overall symptom burden, and impairment in quality of life; the benefits for depression and quality of life persisted at three months. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
Multidisciplinary management for longer-term complications of HCT is discussed separately. (See "Long-term care of the adult hematopoietic cell transplantation survivor", section on 'Coordination of care'.)
HEMATOLOGIC
Cytopenias — Autologous and allogeneic HCT are associated with neutropenia, anemia, and thrombocytopenia in the peri-transplant period. The degree of myelosuppression and the time to hematopoietic recovery are influenced by the preparative regimen, graft source, and the presence of graft-versus-host disease (GVHD).
Transfusion of blood products and use of hematopoietic growth factors are important aspects of care and are discussed separately. (See "Hematopoietic support after hematopoietic cell transplantation".)
Bleeding — Approximately one-quarter of patients experience a hemorrhagic event within the first year after transplantation.
A multicenter study of 789 patients who underwent myeloablative HCT reported that 11 percent of patients had a significant hemorrhagic event in the first 60 days post-transplantation and 2 percent died from a hemorrhagic event [2]. The genitourinary and gastrointestinal tracts were the most common sites for bleeding.
In a single institution study, a hemorrhagic event or life-threatening bleeding were noted in 26 and 9 percent, respectively, of patients who underwent allogeneic HCT; median follow-up in the study was 33 months and most bleeding occurred within the first two years [3]. The most common sites for life-threatening bleeding were pulmonary (16 percent), gastrointestinal (14 percent), and central nervous system (12 percent). Life-threatening bleeding was associated with lower overall survival at three years post-HCT (17 versus 67 percent) and, in multivariate analysis, life-threatening bleeding was associated with severe thrombocytopenia after day 28, grade III to IV graft-versus-host disease, and thrombotic microangiopathy. (See 'Thrombotic microangiopathy' below.)
Blood product support for the bleeding patient is discussed separately. (See "Hematopoietic support after hematopoietic cell transplantation", section on 'Blood product support'.)
Thrombotic microangiopathy — Transplantation-associated thrombotic microangiopathy (TA-TMA; also called post-transplant thrombotic microangiopathy) is a potentially life-threatening complication of transplantation caused by endothelial injury. TA-TMA is manifest as renal dysfunction and/or unexplained neurologic dysfunction, together with evidence of intravascular hemolysis that typically develops 20 to 100 days after transplantation. Evaluation, diagnostic criteria, differential diagnosis, and management of TA-TMA are discussed separately. (See "Kidney disease following hematopoietic cell transplantation", section on 'Thrombotic microangiopathy'.)
The incidence and risk factors for TA-TMA are poorly defined; reports differ, in part, because of various definitions of the syndrome in assorted studies. The cumulative incidence of TA-TMA three years after allogeneic HCT was 3 percent among 23,665 children and adults in a retrospective, registry-based study by the Center for International Blood and Marrow Transplant Research (CIBMTR) [4]. In this study, diagnostic criteria for TA-TMA were not stipulated by the registry; rather, the diagnosis was determined by the treating physician. Overall survival (OS) for patients with TA-TMA was 42 percent at one year and, compared with unaffected patients, those with TA-TMA had higher mortality (hazard ratio 3.1; 95% CI 2.8-16.3). Among patients with TA-TMA, the most common causes of death were organ failure (24 percent), primary disease (22 percent), infection (20 percent), GVHD (19 percent), and hemorrhage/vascular (8 percent). In multivariate analysis, female sex, prior autologous HCT, underlying acute lymphoblastic leukemia/lymphoma or severe aplastic anemia, mismatched or unrelated donor, myeloablative conditioning regimen, and pretransplant kidney dysfunction were identified as independent risk factors.
ORAL MUCOSITIS
Clinical presentation — Oral mucositis (OM) is a major source of morbidity in patients undergoing HCT. OM is typically painful, impairs nutritional intake, adversely affects the quality of life, and may prolong hospitalization and increase hospital costs [5,6]. Severe OM has been associated with a greater risk of 100-day post-HCT mortality [5-7].
Most patients who undergo a myeloablative conditioning regimen develop significant mucositis and have difficulty maintaining adequate caloric intake. Severe OM (grades 3 to 4) is experienced by approximately two-thirds of patients who undergo myeloablative conditioning for HCT [8]. The time course of OM generally peaks between 6 and 12 days after HCT and then slowly resolves over the next 7 to 14 days [9]. Clinical manifestations and grading scales for OM are described separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Clinical manifestations'.)
The pathophysiology of mucositis is complex, and involves direct tissue damage, generation of reactive oxygen species, inflammatory cytokines, and alterations in the microbiome, as discussed separately [10-12]. Cytotoxic agents used in conditioning regimens and patient characteristics that are associated with severe mucositis are discussed separately [8,13-15]. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Mucositis'.)
Studies that reported risk factors for severe mucositis include:
●In a study of patients undergoing allogeneic HCT for chronic myeloid leukemia, adverse risk factors for developing more significant degrees of OM included conditioning regimens utilizing total body irradiation (TBI), a body mass index ≥25, non-use of multivitamins prior to transplantation, and the presence of the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype [13].
●In a study of 197 patients receiving high dose melphalan or BEAM (BCNU, etoposide, cytarabine, melphalan) as conditioning prior to autologous HCT for multiple myeloma or non-Hodgkin lymphoma, severe OM occurred in approximately 45 percent, with a mean duration of 5.3 to 5.5 days [15]. The time from start of conditioning to peak OM was 12 to 15 days; risk factors for severe OM included higher chemotherapy doses and poor performance status.
Management — There is no consensus regarding the optimal approach to prevention and/or mitigation of OM. No randomized studies have compared approaches, and management varies by institutional practice.
Our approach — For patients undergoing myeloablative conditioning with high dose melphalan or TBI, we suggest oral cryotherapy (ice chips swished around the mouth for 30 minutes) at the time of conditioning therapy.
Some experts suggest adding either photobiomodulation (PBM; intraoral low level laser irradiation) or palifermin for patients receiving myeloablative conditioning for autologous HCT and/or allogeneic HCT, because each can modestly reduce OM [9,16,17]. However, neither PBM nor palifermin has been widely adopted, which may reflect limited availability (PBM), expense (both PBM and palifermin), or a lack of benefit in preventing irritation of the rest of the gastrointestinal tract or other transplant outcomes.
Pain management and other aspects of oral care for the patient with OM are described separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Management'.)
Nutritional support for the patient with mucositis is discussed below. (See 'Nutritional support' below.)
Oral cryotherapy — Oral cryotherapy may be a beneficial, cost-effective means of reducing OM in the setting of myeloablative conditioning with high dose melphalan.
We suggest use of oral cryotherapy (ice chips swished around the mouth for 30 minutes) as a simple, cost-effective measure to reduce mucositis, but the benefit appears to be modest. Additional details of oral cryotherapy are presented separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Oral cryotherapy'.)
Use of oral cryotherapy for prevention of OM in patients receiving high dose melphalan, with or without TBI, is suggested by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and National Cancer Center Network (NCCN) [9,16,17].
Photobiomodulation (laser therapy) — Pretreatment with photobiomodulation (PBM) reduces the severity of mucositis in patients undergoing conditioning therapy for HCT.
We consider PBM an acceptable approach for prevention of OM, but it has not been widely adopted because of limited availability and expense. Use of PBM for mitigation of OM is discussed separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Photobiomodulation (low-level laser therapy)'.)
PBM has been recommended in consensus guidelines of MASCC/ISOO to reduce the incidence of OM in patients receiving a myeloablative conditioning regimen for HCT and is supported by the NCCN [9,16].
Palifermin (KGF) — Palifermin (recombinant human keratinocyte growth factor; KGF) can prevent OM in patients undergoing autologous HCT.
We consider that palifermin is an acceptable approach for prevention of OM in HCT, but this benefit must be weighed against the considerable expense, inconvenience of this intravenous medication, and lack of impact on other portions of the gastrointestinal tract. Use of palifermin to prevent or treat mucositis and details of informative studies of palifermin are discussed separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Palifermin'.)
A meta-analysis reported a modest reduction in the risk of moderate to severe mucositis in the transplant setting, but the degree of benefit was uncertain, because the six trials of HCT that were analyzed varied based on type of transplant (ie, autologous versus allogeneic), conditioning regimens, underlying diseases, and other parameters [18]. A randomized, double-blind, placebo-controlled trial did not show any advantage for the use of palifermin, and reported no impact on engraftment, acute graft-versus-host disease (GVHD), or survival [19-21].
Palifermin is approved by the US Food and Drug Administration and the European Medicines Agency to decrease the incidence and severity of severe OM in patients receiving myelotoxic therapy requiring stem cell support. Clinical practice guidelines recommend prophylactic use of palifermin in the setting of autologous HCT and consideration of its use for allogeneic HCT [16,22,23]. Despite these recommendations, many groups do not use palifermin due to its expense and modest benefit.
Other agents
●Other cytokines (eg, GM-CSF, G-CSF, IL-11) – There is no compelling evidence of a benefit for either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) in the prevention or mitigation of OM, based on a systematic review of the literature [18]. MASCC/ISOO clinical practice guidelines specifically suggest not using either parenteral or topical colony-stimulating factors to prevent OM [16].
Interleukin (IL)-11 has cytoprotective effects on the gastrointestinal tract but is rarely used due to toxicity, cost, and limited efficacy. IL-11 has been shown to protect against neutropenic sepsis in animals [24-26]. In a double-blind, placebo-controlled trial in 40 patients undergoing chemotherapy for malignant hematologic diseases, recombinant human IL-11 reduced the incidence of bacteremia (predominantly of enteric origin) [27].
●Glutamine – Supplementation with parenteral glutamine has not been shown to mitigate the incidence or severity of mucositis in HCT. MASCC/ISOO clinical practice guidelines specifically recommend not using parenteral glutamine but considered the evidence on oral glutamine suspension to be insufficient to prompt a recommendation [16]. There are conflicting data regarding a benefit of oral glutamine in other settings of chemotherapy-associated OM, as discussed separately. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Treatments that are not recommended'.)
Use of glutamine for nutritional support is discussed separately. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Glutamine supplementation'.)
●Pentoxifylline – There is no persuasive evidence that oral pentoxifylline (a xanthine derivative used as a drug to treat claudication) is effective for OM associated with HCT, and we suggest that it should not be used in this setting. This suggestion is consistent with MASCC/ISOO clinical practice guidelines [16].
DIARRHEA — There are numerous causes of diarrhea in the setting of HCT, including non-oral mucositis, infections associated with cytopenias, graft-versus-host disease (GVHD), and others. Non-oral gastrointestinal (GI) mucositis may cause pain, nausea/vomiting, and diarrhea.
Evaluation and initial management — There are numerous possible causes of diarrhea in the post-transplantation setting, and management is informed by the severity and underlying cause. Approximately 80 percent of patients will have at least one episode of acute diarrhea within the first 100 days following allogeneic HCT [28].
Assessment should include the quantity and quality of the stool and evaluation for possible causes, even as correction of volume depletion and metabolic derangements is begun. Evaluation is influenced by the duration of diarrhea, age of the patient, and other characteristics, as described separately. (See "Approach to the adult with acute diarrhea in resource-rich settings" and "Approach to the adult with chronic diarrhea in resource-abundant settings" and "Diagnostic approach to diarrhea in children in resource-rich countries".)
Initial management of diarrhea after transplantation is similar to that in the patient who has received chemotherapy, which is presented separately. (See "Management of acute chemotherapy-related diarrhea".)
Causes of diarrhea — There are several distinctive causes of diarrhea in this setting that deserve consideration.
Acute GVHD — Acute GVHD is the most common cause of persistent acute diarrhea following allogeneic HCT, accounting for 64 percent of episodes in one prospective series [28]. Involvement of the GI tract with acute GVHD varies but is generally characterized by abdominal cramping and diarrhea, which may initially be watery with high volumes. The diarrhea frequently becomes bloody, resulting in significant transfusion requirements. While the diagnosis can often be made on clinical grounds, histologic confirmation may be helpful to corroborate a clinical impression of acute GVHD. The diagnosis and management of acute GVHD is discussed in more detail separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease", section on 'Gastrointestinal tract' and "Prevention of graft-versus-host disease".)
Infections — Infectious diarrhea is a less common cause of diarrhea post-HCT but is important to exclude prior to the initiation of immunosuppressive agents for the treatment of presumed GVHD. Common causes of infectious diarrhea in this setting include Clostridioides difficile, cytomegalovirus, adenovirus, and enteric viruses (eg, coxsackie, echovirus, rotavirus, norovirus). Parasitic infections, such as giardiasis, are less common, possibly due to the strict hygienic practices employed by transplant centers. Infections following HCT are discussed in more detail separately. In culture-negative diarrhea where GVHD has been ruled out, occasionally a course of metronidazole is effective. (See "Overview of infections following hematopoietic cell transplantation".)
Non-oral mucositis — Non-oral mucositis from chemotherapy and/or radiation therapy used in the conditioning regimen can affect the entire GI tract and can cause diarrhea.
Cord colitis syndrome — Cord colitis syndrome is a poorly-understood syndrome in recipients of umbilical cord blood (UCB) grafts. Cord colitis is distinguished from other causes of diarrhea by negative viral and bacterial cultures and a colon biopsy that demonstrates chronic active colitis, frequently with associated granulomas.
A case series of 104 patients who underwent UCB transplantation at a single institution described cord colitis syndrome in 11 percent of cases [29]. Patients most commonly presented with a persistent (>7 days) watery, non-bloody diarrhea starting a median of 131 days after HCT. The diarrhea was associated with weight loss (91 percent) and fever (64 percent), and the majority of patients required hospitalization. As with other forms of colitis, computed tomography (CT) demonstrated focal or diffuse thickening of the colonic wall. Colonoscopy revealed erythematous mucosa with or without ulcerations, but no pseudomembranes. All cases demonstrated a response to antibacterial treatment (usually metronidazole with or without a fluoroquinolone) with a median treatment duration of 14 days. While approximately half of the patients relapsed after the discontinuation of antibiotics, all responded to subsequent courses of antibiotics.
Other causes — Other distinctive causes of diarrhea after transplantation include medications (eg, mycophenolate mofetil), mucosal damage due to the conditioning regimen [30], neutropenic enterocolitis [31], and, infrequently, post-transplantation lymphoproliferative disease involving the GI tract [32].
Management of diarrhea — Our suggestions for management of diarrhea are consistent with recommendations of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and National Cancer Center Network (NCCN) [9,16]. Prevention and treatment of nausea and vomiting in patients following HCT are discussed separately. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'High-dose chemotherapy regimens'.)
NUTRITIONAL SUPPORT
Total parenteral nutrition — There is no consensus regarding which patients should receive total parenteral nutrition (TPN) nor agreement about the optimal timing and duration of TPN.
We generally suggest TPN for patients who have mucositis that is severe enough to impair caloric and other nutritional needs by mouth, and we continue it until they are able to maintain adequate nutrition orally [33]. Patients undergoing autologous HCT rarely receive TPN given the likelihood of rapid recovery and high cost of treatment.
Randomized trials have reported both benefits and some potential disadvantages for TPN in the setting of HCT. Findings from studies of TPN after HCT are not always consistent, as exemplified by the following studies:
●A phase 3 trial examined the impact of TPN in 137 patients ≥1 year old with normal nutritional status who were to undergo HCT [34]. Patients were randomly assigned to prophylactic TPN from one week prior to four weeks after HCT versus 5 percent dextrose solution containing electrolytes, minerals, trace elements, and vitamins. After median follow-up of two years (minimum one year), those who received TPN had improved overall survival, time to relapse, and disease-free survival, and total calorie and protein intake. Engraftment, duration of hospitalization, incidence of acute and chronic graft-versus-host disease and bacteremia did not differ between the groups. TPN was ultimately required in 40 of 66 control patients when nutritional depletion was documented.
●In a double-blind trial of 258 patients who were randomly assigned to receive either TPN or hydration in an outpatient setting, those who received TPN had a delay in the resumption of ≥85 percent of their caloric requirement, suggesting that administration of TPN may suppress normal appetite [35]. There was no effect of TPN on hospital readmission, disease relapse, or survival, but patients who received only hydration lost more weight.
The use of TPN for nutritional support in patients undergoing HCT for malignant diseases is discussed separately. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Hematopoietic cell transplantation' and "Nutrition support in critically ill patients: Parenteral nutrition".)
Other nutritional support
●Enteral nutrition – (See "Nutrition support in critically ill patients: Enteral nutrition".)
●Glutamine supplementation – The use of glutamine for nutritional support, either alone or as a supplement to TPN, is discussed separately. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Glutamine supplementation'.)
LIVER DISEASE — Liver dysfunction is common after HCT (especially after myeloablative conditioning) and can range from asymptomatic elevations of serum bilirubin and hepatic enzymes to hepatic graft-versus-host disease, hepatic sinusoidal obstruction syndrome (SOS), and death from fulminant liver failure [36-39]. (See "Clinical manifestations and diagnosis of chronic graft-versus-host disease", section on 'Liver' and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease", section on 'Liver'.)
Hepatic SOS (also referred to as veno-occlusive disease) is a syndrome characterized by painful hepatomegaly, weight gain, ascites, and jaundice, which can progress to fulminant hepatic failure. Diagnosis, treatment, and prevention of hepatic SOS are discussed separately. (See "Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults" and "Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults", section on 'Introduction'.)
RENAL COMPLICATIONS — There are numerous causes of kidney injury following HCT. The prevalence, causes, and management of renal complications after HCT are discussed separately. (See "Kidney disease following hematopoietic cell transplantation".)
PULMONARY COMPLICATIONS — There are numerous causes of pulmonary complications after transplantation. Evaluation of the patient who has undergone autologous or allogeneic HCT is discussed separately. (See "Pulmonary complications after autologous hematopoietic cell transplantation" and "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes".)
PREVENTION OF INFECTION — Patients who undergo HCT are at risk for bacterial, viral, and fungal infections. The types of infection vary with the time from transplantation, autologous HCT (figure 1) versus allogeneic HCT (figure 2), and the degree of immune deficiency and cytopenias [40,41]. (See "Overview of infections following hematopoietic cell transplantation" and "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)
Infection prevention practices (eg, neutropenic precautions, antibiotics, antiviral drugs, antifungal drugs, immune globulin infusions, vaccinations) vary between institutions and are discussed separately. (See "Prevention of infections in hematopoietic cell transplant recipients" and "Induction therapy for acute myeloid leukemia in medically-fit adults", section on 'Monitoring and supportive care during therapy'.)
Guidelines for preventing opportunistic infections in these subjects, cosponsored by the Centers for Disease and Control and Prevention (CDC), Infectious Diseases Society of America (IDSA), and the American Society of Blood and Marrow Transplantation (ASBMT), and a discussion of the use of immunizations in the post-HCT period are presented separately. The IDSA clinical practice guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients, as well as other IDSA guidelines, can be accessed through the IDSA's website [42]. (See "Immunizations in hematopoietic cell transplant candidates and recipients".)
NEURO-PSYCHIATRIC MORBIDITY
●Delirium – Some patients experience an acute confusional state (delirium) after HCT, especially during the first 30 days. Delirium may be associated with complications (eg, aspiration, falls); decreased performance status; longer hospital stays; and may be distressing to the patient, family, and medical team. (See "Diagnosis of delirium and confusional states" and "Delirium and acute confusional states: Prevention, treatment, and prognosis".)
Medications are a common cause of delirium in this setting (table 1). Whenever possible, the number and types of medications should be limited to avoid exacerbating delirium and other complications. Transient, profound delirium with concurrent cardiac and gastrointestinal effects has been reported following infusions of the hematopoietic cell product, perhaps due to encephalopathy from the dimethylsulfoxide (DMSO) used as a cryopreservative [43-45].
In a prospective, single center study, 45 of 90 patients experienced delirium within 30 days of undergoing autologous or allogeneic HCT [46]. Delirium was assessed using standardized rating scales that were administered three times a week and the median duration of delirium was approximately 10 days. Pretransplantation risk factors for severe delirium included metabolic abnormalities (eg, elevated serum creatinine, alkaline phosphatase, or magnesium), total body irradiation, older age, and prior alcohol or substance abuse. Patients who experienced an episode of delirium following myeloablative conditioning, compared with those who did not, had impaired neurocognitive abilities and persistent distress 80 days after HCT [47]. In another study from this group, current or prior pain and use of higher opioid doses were also associated with more severe episodes of delirium [48].
●Psychiatric disorders – Psychiatric issues are relatively common after HCT and are often not diagnosed in the post-transplant setting. Attention to the potential for psychiatric problems is important for the overall well-being of surviving patients [49]. Evaluation and management of depression is described separately. (See "Unipolar depression in adults: Assessment and diagnosis".)
Few studies have prospectively examined psychiatric disorders in patients undergoing HCT. A prospective single institution study of 220 patients undergoing HCT for a hematologic malignancy reported a 21 percent incidence of a psychiatric disorder (eg, depressive, anxiety, or adjustment disorder) at the time of hospital admission for the transplant and an incidence of 22 percent during post-transplant follow-up [50]. Multivariate analysis reported that the risk for a psychiatric disorder was associated with younger age, female sex, past psychiatric history, lower functional status, presence of pain, smoking cessation, and higher regimen-related toxicity. In a prospective study, patients who experience delirium after HCT scored worse on a mental health survey for anxiety, depression, and treatment distress [47].
While the HCT procedure itself can be physically and emotionally stressful, there does not appear to be a substantially increased risk of a long-term psychiatric disorder due to the procedure itself. Psychiatric disorders in longer-term survivors are discussed separately. (See "Long-term care of the adult hematopoietic cell transplantation survivor", section on 'Mental health'.)
INTENSIVE CARE UNIT ADMISSION — Admission to an intensive care unit (ICU) is associated with high rates of mortality, but there is no consensus regarding which patients should be managed in an ICU. Admission to an ICU is more common and ICU mortality is higher in those receiving myeloablative allogeneic HCT than in those undergoing nonmyeloablative allogeneic HCT or autologous HCT [51,52]. (See "Prognosis of cancer patients in the intensive care unit".)
Short-term and long-term overall survival (OS) varies greatly among published studies, but the following factors present at the time of ICU admission were reported to adversely affect survival in more than one study:
●Endotracheal intubation and mechanical ventilation [52-54]
●Use of vasopressors [51,55]
●Presence of multiorgan failure [51,53,56]
●Elevated bilirubin levels [51,52,54]
Decisions concerning which patients are appropriate for ICU care and how long to continue aggressive therapy are complex issues requiring significant deliberation. Our approach is to consider early in the course of care those patients for whom ICU care is not recommended based on shared decision-making with the patient, loved ones, and practitioners who know the patient best. Consultation by intensivists on the appropriateness of ICU care prior to the time when critical interventions are required has been helpful in aligning appropriate care with the expectations of patients and their families [57]. Advance care planning (eg, living will, power of attorney for health care, life-support instructions) should be completed while the patient is competent, to ensure that care is consistent with the patient's wishes. (See "Advance care planning and advance directives".)
The American Thoracic Society (ATS) statement on withholding and withdrawing life-sustaining therapy, as well as other ATS guidelines, can be accessed through the ATS website at www.thoracic.org/statements. Criteria for utilization of the ICU have been developed with the intent of limiting futile care which is often expensive, painful, and ineffective [57]. (See "Withholding and withdrawing ventilatory support in adults in the intensive care unit".)
FUNCTIONAL RECOVERY — The majority of patients who have successfully undergone autologous or allogeneic HCT return to some aspects of a normal lifestyle. (See "Survival, quality-of-life, and late complications after hematopoietic cell transplantation in adults", section on 'Quality of life'.)
A study of 320 patients who responded to a series of questionnaires following transplantation, reported that one year after transplantation approximately 60 percent of patients had returned to work, school, or homemaking and agreed with the statement: "Life has returned to normal" [58]. More than 80 percent of survivors saw a physician once per month or less and 46 percent of autologous HCT patients and 39 percent of allogeneic HCT patients agreed with the statement: "In general, my health is very good to excellent." All transplant-related medications had been discontinued in 43 percent of autologous and 25 percent of allogeneic HCT patients.
Physical and occupational therapy — Most transplant centers offer physical and occupational therapy to patients undergoing autologous or allogeneic HCT in an effort to minimize functional decline, but there is controversy regarding benefits of exercise and/or stress management for patients who have undergone transplantation.
Several small randomized trials have evaluated various forms of physical therapy in this population. A multicenter trial randomly assigned 109 patients who were undergoing autologous HCT for a hematologic malignancy to a high-intensity exercise program versus usual care and reported no beneficial effects on physical fitness, fatigue, and health-related quality of life (HRQoL) [59]. The program measured cardiorespiratory fitness, handgrip strength, general fatigue, and HRQoL and utilized an 18-week supervised high-intensity combined resistance and interval exercise program. A meta-analysis of 11 studies, which included a total of 734 patients, reported that exercise during hospitalization improved measures of quality of life and decreased fatigue [60]. This analysis did not find an impact on psychological wellbeing or distress.
Social and psychological support — Social and psychological support during and after HCT is important for quality of life and other outcomes [61-65]. Management of psychiatric conditions in this setting is discussed separately. (See "Management of psychiatric disorders in patients with cancer".)
A retrospective single institution study reported that overall survival (OS) was superior in patients who had the consistent presence of an in-hospital lay care-partner [63]. Spouses and parents constituted 61 and 34 percent of care-partners who were present at the bedside during the patient's hospitalization for ≥7 hours/day at least five days/week. Rates of one-year OS were 75 percent versus 26 percent, respectively (hazard ratio 3.1; 95% CI 1.9-4.9).
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The coronavirus disease 2019 (COVID-19) pandemic has increased the complexity of cancer care. Important issues include balancing the risk from treatment delay versus harm from COVID-19, ways to minimize negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited health care resources. Additionally, immunocompromised patients are candidates for a modified vaccination schedule (figure 3), other preventive strategies (including pre-exposure prophylaxis), and the early initiation of COVID-directed therapy. These issues and recommendations for cancer care during the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")
SUMMARY
●Early complications – Patients who undergo hematopoietic cell transplantation (HCT) are subject to numerous complications in the first year after transplantation that influence the duration of hospitalization, quality of life, longer-term complications, and transplant outcomes.
●Contributing factors – The type of HCT (ie, allogeneic versus autologous), conditioning regimen (ie, myeloablative [MAC] versus reduced intensity conditioning [RIC]), status of the underlying cancer and prior treatments, presence of graft-versus-host disease (GVHD), graft source, and comorbid medical conditions contribute to the type and severity of complications. (See 'Contributing factors' above.)
●Multi-organ effects – Complications can affect nearly all organ systems. Patient care is enhanced by effective communication and coordination among various specialists, including palliative medicine. (See 'Multidisciplinary care' above.)
●Hematologic – Cytopenias may be associated with risks of bleeding and infections; occasionally patients develop transplantation-associated thrombotic microangiopathy (TA-TMA). (See 'Hematologic' above.)
●Mucositis – Oral mucositis (OM) is a major source of morbidity and is typically painful, impairs nutritional intake, adversely affects quality of life, and may prolong hospitalization. For patients undergoing MAC, we offer oral cryotherapy (ice chips swished around the mouth for 30 minutes). (See 'Oral mucositis' above.)
●Nutritional support – We offer total parenteral nutrition (TPN) for patients who are expected to have significantly impaired oral intake from mucositis, nausea, vomiting, or diarrhea. TPN should continue until the patient can maintain adequate nutrition orally. Use of TPN and selection criteria for patients vary among institutions. (See 'Total parenteral nutrition' above.)
●Liver – Liver dysfunction is a common complication of HCT (especially with MAC) and can range from asymptomatic elevations of serum bilirubin and hepatic enzymes to hepatic GVHD, hepatic sinusoidal obstruction syndrome (SOS), and death from fulminant liver failure. (See 'Liver disease' above.)
●Infections – Patients are at risk for bacterial, viral, and fungal infections, which vary according to the type of transplantation (ie, autologous (figure 1) versus allogeneic (figure 2)), time since HCT, degree of immune deficiency, and severity of cytopenias. (See 'Prevention of infection' above.)
Management of infection prophylaxis during periods of increased risk is discussed separately. (See "Prevention of infections in hematopoietic cell transplant recipients" and "Induction therapy for acute myeloid leukemia in medically-fit adults", section on 'Monitoring and supportive care during therapy'.)
●Neuropsychiatric – Delirium, anxiety, and depression are common and can impair the quality of life and other outcomes. Most patients are able to return to some or all aspects of their previous lifestyle. (See 'Neuro-psychiatric morbidity' above.)
